Ketone bodies are chemical compounds which are produced when fatty acids are metabolised by the body for energy. Ketone bodies themselves can also be used for energy.
The intake of compounds that boost the levels of ketone bodies in the blood can lead to various clinical benefits, including an enhancement of physical and cognitive performance. As disclosed in WO 2004/108740, 3-hydroxybutyl 3-hydroxybutyrate is an example of such a compound that can be administered as a food additive.
3-Hydroxybutyl 3-hydroxybutyrate possesses two stereogenic centres in its structure, which means that there are four distinct stereoisomers of the compound: two diastereoisomers, both consisting of a pair of enantiomers. Published syntheses of this compound produce a mixture of all four stereoisomers but, of these four, the (3R,3′R) isomer is the most effective precursor of (3R)-hydroxybutyrate (‘D-3-hydroxybutyrate’), an important member of the ketone bodies biosynthesised and utilised in vivo. A convenient means of producing this compound in enantiomerically enriched form is therefore required.
In addition to the general routes disclosed in WO 2004/108740, various synthetic approaches have been developed for the production of the desired stereoisomer. As a bench-mark, a classical synthesis, from poly[(3R)-hydroxybutyric acid], gives pure product but involves six chemical steps. Other synthetic strategies have various technical drawbacks including low yields, the production of impure product, or impracticability on a large scale.